This proposal is for the renewal of a grant to train graduate and post-doctoral students in computational biology. Over the last 10 years, the University of Pennsylvania has built a strong program for training students in genomics, bioinformatics and computational biology. The training program of this grant is part of a larger training program that also embraces four different undergraduate concentrations in mathematical and computational biology and a Master's program in Bioinformatics, and which occurs in the context of a strong collaborative research effort spanning the many disciplines involved in computational biology. Current problems in computational genomics, such as trying to understand regulatory mechanisms, require combining disparate sources of knowledge such as gene expression, promoter region and intron structure and function, and comparisons across multiple organisms. Such research requires deep understanding of the biology of the organism or phenomenon being studied, and of the experimental techniques and statistical and algorithmic methods available. The purpose of this grant is to train students with these skills and to produce researchers who will be able to address current and future research needs in computational biology. Penn has made tremendous progress in computational biology training in the last few years, as was hoped by the authors of the original training grant proposal. Penn now has a new Graduate Group, Genomics and Computational Biology (GCB) within the Biomedical Graduate Studies (BGS) program in the School of Medicine (SOM), into which we took 8 PhD (including one MD/PhD) students last year, and have 7 PhD students accepted for matriculation in the fall of 2003. While it is envisioned that graduate training support from this grant will be increasingly focused on students in GCB, we plan to continue.supporting PhD students and post docs in the Biology and the Computer and Information Science (CIS) departments, as well as in the School of Medicine. We have also added new courses serving these students, and hired two new faculty members in computational biology. Most Genomics activities at Penn fall under the umbrella of the Penn Genomics Institute (PGI). PGI provides a wide variety of computational and experimental resources including microarry facilities, proteomics facilities, hardware and software for bioinformatics, and training and consulting. All students funded by this grant will have access to these facilities. PGI includes the Penn Center for Bioinformatics (PCBI), which although mainly a research center, is significantly involved with the training program. For example, in their first year, GCB students are housed in PCBI, and students will do research rotations with PCBI faculty.